DESCRIPTION (Verbatim from the Applicant's Abstract): During the past few years, numerous in vivo brain proton (1H) magnetic resonance spectroscopy (MRS) Studies have suggested a correlation between pathology and the observable metabolite levels in cancer, epilepsy, Alzheimer's disease, multiple sclerosis, HIV infection, stroke and other disorders of the central nervous system. Unfortunately 1H-MRS still suffers from (a) low voxel signal-to-noise ratio at the desired, sub 1 ml, spatial resolution obtained at a "clinically reasonable" 40 min. session; (b) spectral contamination by signals from extraneous tissue, due to limitations of current localization methods, especially at high, >3 Tesla, magnetic fields; and (c) scarcity of software to design and interpret results from these experiments. To address these, the first goal of this project is to develop and optimize echo and non-echo 3D localization methods based exclusively on Hadamard spectroscopy imaging (HIS). Using 3D HIS in all directions with either surface or volume-coils will: (a) improve the voxels' profile, hence, intervoxel isolation; (b) intrinsically suppress extraneous contamination; (c) be simple to implement, post-process and display; (d) be suitable for 1H-MRS even at very high, >3 T, magnetic fields, i.e., immune to the chemical shift artifacts associated with selective-pulses; and (e) require fewer encoding steps, thus, execute faster than chemical-shift-imaging based methods. The second goal is to produce platform-independent image-guided radio-frequency pulse-design and data post-processing software for the first goal. The purpose and guiding philosophy is to ensure that the deliverables from this project: pulse-timing sequence templates, pulse design tools, post processing and display software, can be straightforwardly implemented on any modern imager and computing platform. This work will extend both the clinical and biomedical research applications of 1H-MRS by providing increased spatial resolution, shorter acquisition time and 3D localization sequences suited for clinical, <2 Tesla, as well as high, >3 T, magnetic fields. The development will support ongoing studies investigating changes in brain metabolites associated with multifocal and diffuse brain disorders, specifically, multiple-sclerosis, aging, brain trauma, AIDS and pediatric neurodegenerative diseases.